Lymphocyte Specificity to Protein Antigens. IV. In Vivo and In Vitro Activation of Cytochrome-Specific T Cells Is Dependent on Protein Conformation*

ABSTRACT: Data are presented that suggest that the activation of cytochrome c-specific T lymphocytes is dependent on the integrity of the three-dimensional structure of the protein antigen. These results were obtained both at the population level and at the clonal level. The capacity of the native and denatured forms of cytochrome c to activate a different set of T cell clones was observed both in vivo and in vitro. These results could be explained by the differential capacity of macrophages to process and/or present the two forms of cytochrome c .     

Allergic contact dermatitis due to sesquiterpene lactones

Several compounds containing the α-methylene-γ-butyrolactone moiety have been tested on human volunteers and on guinea-pigs; the animals were experimentally sensitized by alantolactone, iso-alantolactone and laurel oil. Of the two new lactones, spirolactone was the more reactive: this was confirmed by both animal and human testing. The synthetic lactones are less reactive than natural ones. α-Methylene-γ-butyrolactone itself does not elicit cross-reactions in guinea-pigs sensitive either to alantolactone or to isoalantolactone, or in patients sensitive to sesquiterpene lactones. The α-methylene-γ-butyrolactone group is necessary for cross-reaction, but to be active, it has first to be substituted. It was also found that isoalantolactone, allegedly not allergenic, is in fact a sensitizer and cross-reacts with alantolactone. The cross-reaction between laurel and Frullania, found in man, also occurs in guinea-pigs. It is more evident when sesquiterpene lactone is the sensitizer and laurel used to elicit reaction.     

Behcet's Syndrome

Behcets syndrome is a multisystem disease which may produce not only the original triad of relapsing iridocyclitis and recurrent oral and genital ulceration but also skin, central nervous system, joint and gastrointestinal disease. A fatal outcome is uncommon but may occur when the central nervous system or the gastrointestinal tract is involved. We present a patient with colonic ulceration progressing rapidly lo free perforation and generalized peritonitis successfully treated by emergency resection.     

Lack of Physiological Adaptation of the Atrioventricular Interval to Heart Rate in Patients Chronically Paced in the AAIR Mode

Seventeen consecutive patients, aged 56 +/- 12, were chronically paced in the AAIR mode for a symptomatic sinus node disease with atrial chronotropic incompetence defined by a peak exercise heart rate (HR) less than 75% of the maximal predicted heart rate (MPHR) mean = 65 +/- 10%). Sensors used were activity sensing (n = 7), minute ventilation (n = 6), or respiratory rate (n = 4). Basic pacing rate was programmed at 71 +/- 5 beats/min and the maximal sensor rate at approximately 85% MPHR (143 +/- 10); other sensor parameters were programmed individually. Six months after implant, two standardized and symptom limited exercise tests were performed in random order, AAI and AAIR modes, respectively. AAIR pacing significantly improved peak exercise HR (139 +/- 14 vs 112 +/- 30 beats/min; P less than 0.01), maximal sustained workload (132 +/- 42 vs 110 +/- 38 watts; P less than 0.02), and total exercise duration (724 +/- 299 vs 594 +/- 245 sec; p less than 0.02) compared to the AAI mode. In all 17 patients, HR was continuously sensor driven in the AAIR mode, making it possible to precisely study the adaptation of the stimulus-R interval and of the stimulus-R:RR ratio during exercise. Six patients normally adapted with a progressive shortening. Six others did not adapt at all without any variation of interval. Five patients paradoxically increased their stimulus-R interval (286 +/- 10 msec at peak E vs 220 +/- 19 msec at rest) and their stimulus-R:RR ratio (67 +/- 20% vs 29 +/- 4%), producing P waves occurring immediately after, or even within the R wave of the preceding cycle; two patients complained of severe exercise related symptoms corresponding to the so-called "AAIR pacemaker syndrome." The principal factors involved in the nonadaptation of AV interval to HR were related to the patient (organic heart disease, with the particular problem of the denervated heart; the bradytachy syndrome; and the use of drugs, especially beta blockers and Class I antiarrhythmic drugs) or to the pacemaker ("overstimulation" phenomenon). These observations constitute an additional argument for wider indications of implanting DDDR units in these patients.     

Surgical Interruption of a Left Inferior Vena Cava Following the Transfemoral Implantation of a Permanent Pacing Lead

This report describes the case of a patient in whom, after an unsuccessful attempt through the subclavian vein, a permanent pacing lead was inserted through the femoral vein and a left inferior vena cava with azygos continuation. The procedure was followed 4 months later by a pulmonary embolism complicating a right femoroiliac thrombosis. The patient was successfully treated by a percutaneous lead extraction procedure combined with an inferior vena caval surgical interruption. (PACE 1997; 20[Pt. I]:1365-1366)     

Triple Chamber Pacemaker for End-Stage Heart Failure in a Patient with a Previously Implanted Automatic Defibrillator

A 63-year-old man with an ischemic dilated cardiomyopathy previously implanted with an implantable cardioverter defibrillator (ICD) received a triple chamber pacemaker as an ultimate therapeutic resort for end-stage congestive heart failure. After implant, the tolerance to physical exercise increased and NYHA class decreased from III to II. Echocardiography assessed ventricular contraction resynchronization during DDD biventricular pacing as compared to VVI pacing. No major pacemaker-ICD interaction was noted during testing or follow-up. We conclude that sequential biventricular pacing is feasible in the presence of an ICD.     

Permanent Left Ventricular Pacing With Transvenous Leads Inserted Into The Coronary Veins

This paper describes a preliminary experiment - conducted jointly by 2 centers - of permanent left ventricular pacing using leads inserted by the transvenous route and through the coronary sinus into the cardiac veins of the left ventricle free wall. The aim was to obtain permanent biventricular pacing in a totally endocavitary configuration in pattents with severe LV dysfunction and drug-refractory heart failure. Two types of leads were used: nonspecific unipolar leads at the beginning of the experiment, followed by leads specifically designed to be used in the coronary sinus in a second step. The electrode could be fitted in an adequate location in 35 of the 47 patients (75.4%), with a 1.15±0.7 V acute pactng threshold and 11.8±5.7 mV R wave amplitude. The success rate was significantly higher with the specific electrodes (81.8% vs 53,3%, p < 0.001). The pacing and sensing thresholds upon implantation were not influenced by the type of lead or by the localization of the cardiac vein that was catheterized (great cardiac vein, lateral vein, postero-lateral or posterior vein, mid cardiac vein). In contrast, the pacing threshold was significantly lower (0.8 ± 0.2 vs L8 ± 0.8 V; p = 0.002) and the R wave amplitude tended to be greater (13.1 ± 4.5 mV vs 9.3 ± 6.5 mV; p = 0.07) when the tip electrode could be inserted distally into the vein, by comparison with a proximal site near the ostium. At the end of follow-up (10.2 ± 8.7 months), 34 out of the 35 leads were still fully functional, with a chronic pacing threshold of 1.8 ± 0.7 V and a R wave amplitude of 10.7 ± 6 mV. To conclude, permanent LV pacing via the transvenous route is possible in most patients, with excellent safety and long-term results.     

Initial and Long-Term Evaluation of Escape Rhythm After Radiofrequency Ablation of the AV Junction in 50 Patients

Between 1986 and 1994, 50 patients (mean age 63 ± 13 years), 25 of whom had organic heart disease and presenting with atrial arrhythmias refractory to 5.6 ± 1.6 antiarrhythmic drugs, underwent radiofrequency ablation (5 ± 3 pulses by procedure; duration of pulses 50.5 ± 32 s) of the proximal AV junction to create complete and permanent AV block. The escape rhythm was studied immediately after the procedure and during long-term follow-up. Immediately after the procedure, an escape rhythm was observed in 80% of the patients (junctional in 92%). Over a mean follow-up of 36 ± 16 months in 47 patients (2 patients died before assessment of escape rhythm and 1 was lost to follow-up), an escape rhythm was present in 39 patients (83%) and absent in the remaining 8 (17%). The only significant difference between the two groups was the initial presence of an escape rhythm (P = 0.008). However, three patients with an initial escape rhythm had none during long-term follow-up. The initial presence of an escape rhythm as a predictive factor of its presence during follow-up had a sensitivity of 87%, specificity of 63%, positive predictive value of 92%, and negative predictive value of 50%. Thus, the absence of an escape rhythm during long-term follow-up causing pacemaker dependency was noted in 1 of 6 patients. This represents a limitation to this palliative treatment, which should be reserved for patients suffering from supraventricular tachycardias refractory to other treatments.     

IMMUNOHISTOCHEMICAL DETECTION OF p53 PROTEIN OVEREXPRESSION VERSUS GENE SEQUENCING IN URINARY BLADDER CARCINOMAS

PURPOSE: Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS: 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS: The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS: The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.